61 research outputs found

    Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study)

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    OBJECTIVE: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. METHODS: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at −15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. RESULTS: Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = −1.4 %, 95%CI = (−7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. CONCLUSION: Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. KEY POINTS: • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up

    Entwicklung von Biosensoren für die biotechnologische Praxis

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    Zur Verbesserung biotechnologischer Prozesse ist es notwendig, die wichtigsten Schlüsselkomponenten in den Kultivierungsmedien zu überwachen und zu regeln. Voraussetzung dafür ist die In-situ- und On-line-Messung dieser Größen. Dazu müssen die Analyseninstrumente an den Produktionsreaktor direkt angekoppelt werden. Wegen des hohen Preises dieser Instrumente würde die Ausstattung eines jeden Reaktors mit einem Analysensystem sehr aufwendig und teuer. Hier können die einfachen und preisgünstigen Biosensoren Abhilfe schaffen. Biosensoren bestehen aus einem chemisch-spezifischen Empfänger (Enzym, Antikörper, Zelle), der mit einem sog. Transducer verbunden ist. Der Transducer ist ein physikalischer Sensor, der die chemischen Änderungen in der Empfängerschicht in Licht- oder elektrische Signale umwandelt. Abhängig davon, welchen physikalischen Sensor man verwendet, unterscheidet man zwischen - potentiometrischen, amperometrischen, kalorimetrischen, optischen und mechanischen Sensoren. Im Institut für Technische Chemie (TCI) der Universität Hannover werden potentiometrische, kalorimetrische und optische Sensoren entwickelt und zur Überwachung und Regelung biotechnologischer Prozesse eingesetzt. Daher werden hier nur diese Sensoren behandelt

    High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in France and characterization of biochemical and clinical features.

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    International audiencePURPOSE:To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report six novel mutations, to characterize the biochemical features of a recurrent novel mutation and to study the clinical features of adRP patients.DESIGN:Retrospective clinical and molecular genetic study.METHODS:Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot.RESULTS:We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1 to 0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families.CONCLUSIONS:The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases which could be underdiagnosed

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

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    Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

    Effect of seed treatment with putative defence priming chemicals on defence-related gene expression and pathogen resistance in Norway spruce (Picea abies) seedlings

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    Chemical seed treatment may be a simple method to protect conifer seedlings from pests and pathogens in plant nurseries and forest stands. In this study, I tested the ability of eight putative defence priming chemicals (methyl jasmonate (MeJA), β-amino butyric acid (BABA), hexanoic acid, gibberellic acid, quinic acid, thiamine, riboflavin and chitosan) to enhance the resistance of Norway spruce (Picea abies) seedlings by means of seed treatment. I carried out two different tests on young spruce seedlings grown from seeds soaked overnight in priming chemicals: I tested (1) 10-day-old seedlings for resistance to the oomycete Pythium ultimum, and (2) 10-week-old seedlings for expression of selected defence-related genes (ACS, LOX, PAL1, TPS-Car and Chi4) after mechanical wounding. In addition, I measured germination rates of treated seeds and root length of 8-day-old seedlings grown from treated seeds. None of the seed treatments I tested caused significant changes in seedling resistance to P. ultimum, gene expression, or the percentage of seeds that germinated. All seed treatments significantly accelerated seed germination, except from BABA (0.1 mM and 0.5 mM), quinic acid (0.1 mM) and riboflavin (0.5 mM). Seed treatment with MeJA (0.05 mM and 0.1 mM) led to a significant decrease in seedling root length, while treatment with BABA (0.5 mM) and gibberellic acid (0.1 mM and 0.5 mM) led to an increase in root length. Overall, I could not demonstrate that any of the tested seed treatments has the potential to enhance the resistance of young spruce plants. My results do illustrate the importance of evaluating fitness costs in studies on seed priming.M-ECO

    Effect of seed treatment with putative defence priming chemicals on defence-related gene expression and pathogen resistance in Norway spruce (Picea abies) seedlings

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    Chemical seed treatment may be a simple method to protect conifer seedlings from pests and pathogens in plant nurseries and forest stands. In this study, I tested the ability of eight putative defence priming chemicals (methyl jasmonate (MeJA), β-amino butyric acid (BABA), hexanoic acid, gibberellic acid, quinic acid, thiamine, riboflavin and chitosan) to enhance the resistance of Norway spruce (Picea abies) seedlings by means of seed treatment. I carried out two different tests on young spruce seedlings grown from seeds soaked overnight in priming chemicals: I tested (1) 10-day-old seedlings for resistance to the oomycete Pythium ultimum, and (2) 10-week-old seedlings for expression of selected defence-related genes (ACS, LOX, PAL1, TPS-Car and Chi4) after mechanical wounding. In addition, I measured germination rates of treated seeds and root length of 8-day-old seedlings grown from treated seeds. None of the seed treatments I tested caused significant changes in seedling resistance to P. ultimum, gene expression, or the percentage of seeds that germinated. All seed treatments significantly accelerated seed germination, except from BABA (0.1 mM and 0.5 mM), quinic acid (0.1 mM) and riboflavin (0.5 mM). Seed treatment with MeJA (0.05 mM and 0.1 mM) led to a significant decrease in seedling root length, while treatment with BABA (0.5 mM) and gibberellic acid (0.1 mM and 0.5 mM) led to an increase in root length. Overall, I could not demonstrate that any of the tested seed treatments has the potential to enhance the resistance of young spruce plants. My results do illustrate the importance of evaluating fitness costs in studies on seed priming
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